Perinatal exposures may lead to increased risk of childhood cancers, as well as those later in life. Preconceptional parental, transplacental, and/or neonatal exposures may be involved. Studies with animal models are utilized to increase understanding of underlying cellular and molecular mechanisms. Transmammary neonatal exposures have received relatively little attention. We have studied exposure by this route to the carcinogenic nitrosamine, N-nitrosodimethylamine, which is present in tobacco smoke and other environmental sources. After administration to lactating rat mothers, N-nitrosodimethylamine caused formation in tissues of suckling infants of a DNA adduct known to be associated with tumor initiation. Furthermore, if the mother received ethanol at the same time, there was a 10-fold increase in these adducts in some tissues. These results indicate that transmammary exposures should receive further study. Another understudied exposure issue is that of transgenerational carcinogenesis. We are examining the effects of paternal exposure to chromium(III), a chemical widely encountered occupationally. Exposure of male mice to this chemical before mating leads to increased incidence of several types of neoplasms in the offspring. Preliminary results indicate that this is associated with changes in serum hormones in the offspring, and altered expression of a number of hepatic genes as studied by microarray, including insulin-like growth factor binding protein 1. AIDS Title: